Cancer is the leading cause of death. Current therapies for cancer comprise combinations of principal surgical therapy with radiation therapy and chemotherapy. Furthermore, the current therapies comprise applying a similar therapy to all patients having the same type and the same stage of a cancer. At least 40% of the patients fail a primary therapy and thus are subjected to a series of further therapies. If the patients again fail the therapies, cancer metastasis takes place, finally resulting in an increased possibility of death. Thus, the current radiation therapy and the chemotherapy are unable to compatible with various types of cancers or individual cancer patients, and the surgical therapy itself is also currently insufficient for complete cure of cancers in almost all cases.
Various antibody drugs targeting antigen proteins on cancer cells for treatment of cancers have appeared throughout the world as a technique for overcoming the above-described problems of cancer therapies. Specific examples are as follows. It has been demonstrated that HERCEPTIN (registered trademark) comprising as an active ingredient a monoclonal antibody specifically binding to Her2, the sales of which were approved in 1998 as a therapeutic agent for patients with metastatic breast cancer, has such a clinical effect that HERCEPTIN can decrease the number of death of recurrent and metastatic breast cancer patients among Her2-overexpressing metastatic breast cancer patients. It has also been demonstrated that HERCEPTIN does not cause any severe side effects other than cardiac toxicity compared with conventional chemotherapeutics. As another noteworthy feature, the therapeutic effects of a combined use of HERCEPTIN with chemotherapeutics against breast cancer have been demonstrated (Patent Literatures 1-3). However, most antigenic proteins on cancer cells to be targeted by antibody drugs such as Her2 are also expressed in normal cells, so that not only cancer cells but also normal cells expressing antigens are also cytotoxically impaired by administration of antibodies. The resulting side effects may cause for concern.
Cytoplasmic- and proliferation-associated protein 1 (CAPRIN-1) is expressed when normal cells at the resting phase are activated or undergo cell division, and it is an intracellular protein known to form intracellular stress granules with RNA within cells, so as to be involved in mRNA transport and translational regulation. Meanwhile, many other names that represent CAPRIN-1 exist, such as GPI-anchored membrane protein 1 or membrane component surface marker 1 protein (M11S1), as if such proteins had been known to be cell membrane proteins. These names originated from a report that the gene sequence of CAPRIN-1 is a membrane protein having a GPI-binding region and expressed in colorectal cancer cells (Non-patent Literature 1). However, the gene sequence of CAPRIN-1 provided in this report was later revealed to be wrong. The following has recently been reported; i.e., deletion of a single nucleotide in the gene sequence of CAPRIN-1 registered at GenBank or the like causes a frame shift, so that 80 amino acids are lost from the C-terminus, resulting in generation of an artifact (74 amino acids) which corresponds to the GPI-binding portion in the previous report, and additionally, another error is also present 5′ of the gene sequence, so that 53 amino acids were lost from the N-terminus (Non-patent Literature 2). It has been also recently reported that the protein encoded by the gene sequence of CAPRIN-1 registered at GenBank or the like is not a cell membrane protein (Non-patent Literature 2).
In addition, on the basis of the report of Non-patent Literature 1 that CAPRIN-1 is a cell membrane protein, Patent Literatures 4 and 5 describe that CAPRIN-1 (as a cell membrane protein) under the name of M11S1 can be used as a target of an antibody medicine in cancer therapy, although working examples do not describe treatment using an antibody against the protein. However, as reported in Non-patent Literature 2, it has been commonly believed from the time of the filing of Patent Literature 4 to date that CAPRIN-1 is not expressed on the surface of a cell. The contents of Patent Literatures 4 and 5 based only on incorrect information that CAPRIN-1 is a cell membrane protein should not clearly be understood as common general knowledge for persons skilled in the art.